In the field of ophthalmic surgery, it is known to use excimer laser photoablative refractive keratectomy to sculpt the cornea of the eye in order to relieve refractive errors (e.g. myopia) and a number of corneal conditions and diseases. Specifically, the 193 nm argon fluoride excimer laser is able to discretely remove corneal tissue by photoablation without thermal damage to surrounding tissue.
Of major concern is the activation of the stromal keratocytes when a wound is made to the stroma. As is well known, the basic response of wounded tissue is to repair the defect and therefore the ophthalmic surgeon when using this technique is confronted with alteration to the biochemistry, morphologic features and tissue function unpredictability brought about by the wound itself and the healing phenomenon.
Therefore, even though excimer laser ablation of corneal tissue appears to be an efficient method of removing tissue with minimal damage to adjacent areas, nevertheless the healing process does not always lead to the preservation of transparent corneal tissue.
Previous methods of overcoming this problem have been: application of topical steroids such as prednisolone, prednisolone acetate, prednisolone sodium phosphate, fluoromethalone, fluoromethalone acetate, hydromesterone, dexamethasone, and dexamethasone alcohol. Other compounds tested have been idoxuridine, collagen crosslinkage inhibitors and mitomycin C.
It is an object of this invention to ameliorate the known disadvantages of present techniques when dealing with the wound repair mechanism following photoablative refractive keratectomy.
Interferons are a heterogeneous group of proteins that can inhibit many aspects of the fibrotic response. Originally identified by their well known ability to interfere with the production of viral RNA and protein, they also exert anticellular activities generally considered to be inhibitory, which maybe due to their ability to inhibit the c-myc proto-oncogene. Type I interferon (viral interferon, interferon-.alpha. and -.beta.) is produced in response to viral infection, and type II (immune interferon, interferon-.gamma.) in response to specific antigens or mitogens. Of the different classes, .alpha.-interferon is secreted by leukocytes, .beta.- by fibroblasts and .gamma.- by stimulated lymphocytes. Interferons, particularly interferon-.alpha., have been successfully used in humans for twenty years for the treatment of systemic malignancy.
Considerable interest has recently been shown in the potential of interferon as a treatment for such fibrotic diseases as systemic sclerosis, pulmonary fibrosis and keloid. Fibroblasts are stimulated to produce interferons by many cytokines that mediate wound healing, such as interleukin-1-(IL-1), platelet derived growth factor (PDGF) and tumour necrosis factor (TNF). Interferons inhibit fibroblast chemotaxis and proliferation as well as collagen production, the latter synergistically with TNF-.alpha.. Intraperitoneally implanted foreign bodies in mice suffered less encapsulation in the presence of interferon-.gamma., the capsules having a reduced collagen content. Fibroblast glycosaminoglycan production is inhibited by interferon-.alpha., while collagenase production is increased. This deactivation of activated fibroblasts can persist for a long time after a brief exposure to interferon. Of the different types of interferon, the .alpha.- and .beta.-subclasses exhibit a broader antifibrotic spectrum.
The present inventors have recently demonstrated that interferon-.alpha. inhibits foetal calf serum and platelet derived growth factor induced proliferation of human tenon's capsule fibroblasts in vitro. They suggest that interferons may prove to be of benefit in the treatment of fibrosis following PRK in particular, and of ocular fibrosis in general.